How Tumors Respond to Hypoxia
Researchers investigate whether oxygen deprivation promotes or prevents tumor growth
Cancer biologists have long debated whether oxygen deprivation, aka hypoxia, promotes tumor growth or prevents it. Now, a study published in March 2021 in Nature Communications finds evidence for both outcomes—tumor cells deprived of oxygen stop growing in the short term, and over longer periods of hypoxia, the tumors begin to grow and metastasize.
To find out, the researchers measured transcriptional changes to the RNA of tumor cells in cell culture maintained under normal or hypoxic conditions using a combination of precision nuclear run-on sequencing (PRO-seq), RNA-seq, and chromatin immunoprecipitation followed by sequencing (ChIP-seq) technologies.
They sequenced hundreds of transcription factors known as hypoxia-inducible factors (HIFs) that get activated in response to oxygen deprivation. By comparing their sequences to ones in publicly available genetic datasets, the researchers were able to uncover the functions of many of these HIFs.
The analysis revealed a context-dependent response to hypoxia. Acute oxygen deprivation suppresses tumor growth as tumor cells work to preserve their nutrients and oxygen, the researchers report. However, chronic exposure to low oxygen conditions—analogous to advanced malignancies—promotes tumor growth, as cells in search of oxygen migrate and invade nearby tissue.
According to the researchers, the results highlight the need to develop inhibitors to particular HIFs that are associated with poor prognosis across diverse cancer types.